Summary MATERIALS AND METHODSWe examined autoregulation of cerebral blood flow (CBF) over the range of oxygen tension commonly observed in the chronic fetal lamb preparation. Seventeen animals were surgically prepared under general anesthesia for chronic in utero studies. ~a s e d on measured resting arterial Po2 and calculated % saturation 24-48 h after surgery, two groups were defined: a normoxic group of eight with saturation of 57% or higher (our laboratory normal for physiologically stable preparations) and an hypoxic group of nine with saturation less than 57%. Regional CBF was measured with radiolabeled 15-pm microspheres. Autoregulation of CBF was assessed by measuring the change in CBF when fetal mean arterial blood pressure (MABP) was acutely decreased and increased by withdrawal and reinfusion of fetal blood. In normoxic animals CBF was constant over an MABP range of 42-61 torr in all four areas of the brain examined: cerebral hemispheres, basal ganglia, cerebellum, and brain stem. In hypoxic animals CBF was pressure dependent in all areas over an MABP range of 46-73 torr, i.e., autoregulation was abolished. These studies demonstrate that the mechanism of autoregulation is functionally developed in the mature fetal lamb, but operationally dependent upon arterial oxygen concentration. Below a saturation of approximately 50-60% CBF varies directly with perfusion pressure. AbbreviationsBP, blood pressure CBF, cerebral blood flow cpm, count per min i.d., internai diameter MABP, mean arterial blood pressure rCBF, regional cerebral blood flow Impairment of cerebrovascular autoregulation is now generally believed to be an important pathophysiologic mechanism in the genesis of hypoxic and hemorrhagic brain injury of the newborn (10, 20). The theoretical model states that with impairment of autoregulation the cerebral microcirculation is rendered vulnerable to changes in arterial blood pressure. Systemic hypotension results in ischemic cerebral blood flow (CBF) and cerebral infarction, whereas hypertension leads to cerebral hyperemia, rupture of poorly supported capillaries in the vulnerable subependymal germinal matrix, and cerebral hemorrhage (10, 15).Impaired autoregulation has been demonstrated in the severely asphyxiated fetal lamb (12) and in sick human newborns (1 1). The well oxygenated newborn lamp has been shown to autoregulate (16), and there is evidence that the normoxic fetal lamb has at least partial autoregulatory control of CBF (19). But the functional maturity of the autoregulatory mechanism in the fetal lamb, and its sensitivity to hypoxia, have not been clearly established.The present studies were designed to examine autoregulation in utero in the near term fetal lamb, and to determine its stability over the range of arterial oxygen tension normally encountered in chronically prepared laboratory animals.We studied 17 near term fetal lambs estimated to be 130-140 days gestation. Our methods for fetal studies in the chronically prepared sheep have been described in previous publications (12, ...
Using a chronic sheep preparation, with induced foetal acidosis, the effects of low and high dose thiopentone and ketamine on maternal and foetal cardiovascular dynamics were studied. Ketamine 4 mg. kg -t and thiopentone 10 rag. kg -I were both associated with marked reductions in foetal cerebral blood flow and cerebral oxygen delivery. Blood pressure and cerebral blood flow in the acidotic foetus was better preserved, however, following the lower dose of ketamine 2 mg. kg -1 than following thiopentone 6 rag-kg -l. METHODSThe study was approved by our Animal Experimentation Committee as conforming to guidelines for the humane use of animals in research. Fourteen pregnant ewes with single foetuses estimated to be between 130 and 140 days of gestation (term-150 days) were used in the studies. The animals were prepared at least one day before any study in the following fashion. The ewe was anaesthetized with halothane and oxygen, intubated and ventilated to maintain, normal Paco:. A maternal femoral artery and vein were cannulated. The foetus was exposed through a hysterotomy incision, and a foetal axillary artery catheter was passed into the common brachiocephalic trunk. A catheter was also passed into the foetal inferior vena cava through the femoral vein, and a femoral artery catheter was inserted into the abdominal aorta. An inflatable cuff was placed around the umbilical cord. All lines were brought to the skin in the ewe's flank and the incisions were closed. Preparations similar to this have been used successfully in several previous studies from our laboratury. 2.6,7The mother and foetus were allowed to recover for 1-2 days before the study. On the morning of study, maternal and foetal blood gases, acid-base balance and blood pressure were measured. If these values were not in the normal range, the preparation was not used.
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